H2A.Z Acetylation: Deregulation Of Enhancer Activity And 3D Chromatin In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$859,350.00
Summary
DNA is not linear but packaged in the cell nucleus in a three-dimensional (3D) structure in such a way that distal regulatory regions can interact to control gene expression. Our new data suggests that a chemical modification of the histone variant H2A.Z plays a critical role in the formation of the 3D chromatin structure. This project is aimed to dissect the role of H2A.Z in prescribing 3D structure, which will provide a more precise understanding of gene deregulation in cancer.
Transcription At The Centromere: Roles In Formation, Maintenance And Function
Funder
National Health and Medical Research Council
Funding Amount
$549,092.00
Summary
Every human has 46 chromosomes. Chromosomes are structures that carry genes in all our cells. The centromere is an essential component of a chromosome which governs the process of cell division and separation of replicated chromosomes. Defects in centromere function cause abnormalities in cell division that in turn cause a variety of genetic diseases including cancer. We propose to investigate the role that transcription at the centromere plays in determining correct centromere function.
Importance Of Histone Variant H2AZ Acetylation In Gene Activation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$611,737.00
Summary
DNA is packaged in the cell in such a way that essential genes are available to be switched on by the transcription machinery. The packaging involves nucleosomes, that consist of four histone proteins, H2A, H2B, H3 and H4. H2A.Z is a histone variant that is often over expressed in cancer, and therefore could lead to abnormal gene transcription. This project is focused on understanding the role of H2A.Z in gene deregulation in cancer as modification of this mark may provide a potential novel canc ....DNA is packaged in the cell in such a way that essential genes are available to be switched on by the transcription machinery. The packaging involves nucleosomes, that consist of four histone proteins, H2A, H2B, H3 and H4. H2A.Z is a histone variant that is often over expressed in cancer, and therefore could lead to abnormal gene transcription. This project is focused on understanding the role of H2A.Z in gene deregulation in cancer as modification of this mark may provide a potential novel cancer therapeutic target.Read moreRead less
Understanding The Role Of Chromosome Condensation Proteins And Their Link To Disease
Funder
National Health and Medical Research Council
Funding Amount
$601,224.00
Summary
Cells divide through a complex cascade of signals from our genetic material (DNA) which need to be finely tuned for events to occur properly. Errors in control cause faulty cell division and lead to diseases such as cancer. We have identified a master controller of these events termed the condensin complex and aim to understand how it orchestrates these functions by creating a map of its DNA location and understanding which regions in the genetic material it controls and how.
Identifying Novel Long-noncoding RNAs Involved In The Development Of Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$785,204.00
Summary
Recent studies have identified regions within the human genome in which DNA sequence variations are associated with an increased risk of breast cancer. The aim of this proposal is to identify and characterise these non-coding genes that are modulate breast cancer risk. Understanding how sequences variations that alter these novel genes contribute to breast cancer will provide novel avenues for therapy.
Functional Analysis Of Breast Cancer Susceptibility Regions
Funder
National Health and Medical Research Council
Funding Amount
$790,588.00
Summary
Recent studies have identified regions within the human genome in which DNA sequence variations are associated with an increased risk of breast cancer. Several of these regions do not contain any known genes, suggesting that regulatory DNA sequences are responsible for the associated risk. The aim of this proposal is to identify and characterise these DNA sequences. Understanding how sequences variations in these regions contribute to breast cancer will provide novel avenues for therapy.
Understanding The Regulation Of The Location Of Chromosomes Within The Nucleus
Funder
National Health and Medical Research Council
Funding Amount
$333,612.00
Summary
The nucleus of each human cell, despite being under 10µM in diameter, contains 46 chromosomes, each consisting of several centimeters of DNA. The organisation of chromosomes within the nucleus helps regulate which genes are switched on and off. Genes attached to the nuclear lamina, which lines the nuclear membrane, tend to be switched off. Mutations in the nuclear lamina cause several diseases, including progeria, resulting premature aging. I am interested in understanding why only certain regio ....The nucleus of each human cell, despite being under 10µM in diameter, contains 46 chromosomes, each consisting of several centimeters of DNA. The organisation of chromosomes within the nucleus helps regulate which genes are switched on and off. Genes attached to the nuclear lamina, which lines the nuclear membrane, tend to be switched off. Mutations in the nuclear lamina cause several diseases, including progeria, resulting premature aging. I am interested in understanding why only certain regions of the genome attach to the nuclear lamina.Read moreRead less
Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably e ....Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably extend the information potential of the genetic code. In addition, it is now established that chromatin structural features can influence gene expression. In vitro studies support a model in which chromatin functions as a barrier for the access to DNA. Therefore this organization has to be tighly regulated and dynamic to allow the protein-DNA interactions critical for nuclear functions. Importantly genome organisation provides in addition to genetic information another layer of information, so called epigenetic, which by definition means that it is stably inherited throughout cellular divisions, yet it is not encoded genetically. Thus each cell type will display a specific epigenome. We have recently constructed small human minichromosomes, which are much easier to study than the much larger normal chromosomes. The present project proposes to define the epigenetic feature across an entire human chromosome using our minichhromosomes as working models. The outcome will be a significant gain in our knowledge on the processes underlying epigenetic regulation, the organisation of specialised chromatin domain, and behaviour of the chromosomes.Read moreRead less